{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHigh‐mobility group N1 (HMGN1) is a nucleosome‐binding architectural protein that modulates chromatin structure and thereby influences multiple nuclear processes. Notably, HMGN1 regulates the cellular response to DNA damage by promoting the proper recruitment and activation of key repair regulators such as ATM and PARP‑1, partly through controlling histone modifications – for example, facilitating histone H3K14 acetylation and modulating stress‐induced H3 phosphorylation. In embryonic stem cells and differentiated cells, HMGN1 also organizes unstable nucleosomes at transcription start sites, thus contributing to the fidelity of the transcriptional program and maintaining the epigenetic landscape. These chromatin‐regulatory activities are further implicated in the control of cccDNA transcription in hepatitis B models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHMGN1 plays important roles during development and differentiation. In various embryonic contexts, its regulated expression influences cell‐fate decisions – for instance, by modulating the activity of lineage‐defining factors such as Sox9 during chondrogenesis, as well as fine‐tuning the expression of adhesion molecules like N‑cadherin that affect cell motility and aggregation. Moreover, its expression is dynamically controlled during tissue remodeling events such as digit formation, uterine stromal cell decidualization, and hair follicle morphogenesis, while it also affects the chromatin accessibility and transcription factor binding required for proper ameloblast differentiation and enamel mineralization. In contrast, experimental studies indicate that reduced HMGN1 levels do not impair myogenic or adipogenic differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its chromatin‐remodeling functions, HMGN1 serves key roles in immune regulation and the cellular stress response. As a potent alarmin, extracellular HMGN1 triggers Toll‑like receptor 4 signaling to promote dendritic cell maturation, enhance antigen‐specific adaptive immunity, and contribute to antitumor immune responses. This immunomodulatory function is further exemplified by its ability to induce inflammatory mediators in microglial cells via the TLR4/MyD88/NF‑κB pathway, and by its influence on oncogenic programs – for example, by suppressing repressive histone H3K27 trimethylation to facilitate B cell proliferation and leukemia development, as well as by modulating transcriptional amplification in Down syndrome models. HMGN1 has also been implicated in non‐immunologic tumor contexts, wherein its loss may accelerate liver tumorigenesis and contribute to fibrotic processes in the kidney."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yong-Chul Kim, Gabi Gerlitz, Takashi Furusawa, et al. 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